Modified oligonucleotides derived in part from 5'- or 3'-aminonucleosides have potential as tools in diagnostics and antisense research. This potential rests on both the differences and similarities in properties of the modified and natural oligomers. Thus, it has been shown that the highly nucleophilic amino groups of oligomers with terminal aminonucleosides serve as reactive sites for chemical attachment of nucleotide units,.sup.1-7 oligonucleotides,.sup.8-11 and reporter groups.sup.12, and that a terminal 5'-amino group inhibits enzymatic hydrolysis..sup.1 Oligomers with one or more internucleoside anionic 3'P-5'N phosphoramidate links [--OP(O)(O.sup.-)NH--] have been prepared by stepwise coupling to aminooligonucleotides,.sup.1-6 condensation with dimer blocks,.sup.16 chemical ligation on templates, 8-11 and enzymatic synthesis utilizing aminonucleoside triphosphates, templates and primers..sup.13-15 Chemical ligation.sup.8-11 and polymerization.sup.4-6 have also been used to generate internucleoside 3'N-5'P phosphoramidate links. The anionic phosphoramidate derivatives resemble natural oligonucleotides in serving as primers for chain extension by DNA polymerase.sup.14,15 ; however they differ in hydrolytic stability in that the P-N bonds are unusually sensitive to aqueous acids.sup.1,7,15 and are unusually resistant to some restriction enzymes..sup.9-11
The present invention provides novel oligonucleotides having modified internucleoside links and having terminal 3'-amino groups.